Molecular Epidemiological Study on Intratypic Variants of Human Papillomavirus and Risk of Cervical Neoplasia
Date Issued
2011
Date
2011
Author(s)
Chang, Ya-Ju
Abstract
Human papillomavirus (HPV) 16 and 18 are the most oncogenic HPV types worldwide. Other oncogenic HPV 52 and 58 are prevalent in Asia. This study aims to elucidate intratypic variants of HPV 16/18/52/58 and their associations with risk of viral persistence / cervical neoplasia in Taiwan. A total of 11,923 women were enrolled from seven townships in 1991-1992. The HPV DNA in cervical cells was detected and typed by EasyChip HPV blot. Among 807 participants infected with one or more types of HPV 16, 18, 52 and 58, nucleotide variations were determined in cervical cell samples of 653 participants by the polymerase chain reaction sequencing of the long control region (LCR), E6 and E7 genes.
Among 170 and 116 samples determinable for variant analysis of HPV 16 and 18, HPV16 Asian variant and HPV18 Asian-American variant were the most prevalent variants in Taiwan, about 139 (81.8%) and 95 (81.9%) samples, respectively. The large majority of HPV52 and HPV58 samples belonged to HPV52 B variant and HPV58 A3 variant, respectively. Among 280 samples determinable for variant analysis of HPV 52, non-prototype-like variants including lineage B and C were detected in 278 (99.3%) samples. Among 134 samples determinable for variant analysis of HPV 58, the prototype and prototype-like group (lineage A) of HPV58 was found in 132 (98.5%) samples, with sub-lineage A1, A2, and A3 variant in 14.2%, 27.6%, and 56.7%, respectively. It was concluded that frequency distributions of HPV 16, 18, 52 and 58 variants in Taiwan were different from those in European and American populations.
Several previous studies have documented the association between intratypic variants of HPV and risk of cervical neoplasia, but mainly focused on those for HPV type 16. Compared with HPV 16 European variant, the Asian variant was associated with an increased prevalence of cytologically identified high-grade cervical squamous intraepithelial lesion or worse lesions (HSIL+) and histologically confirmed cervical intraepithelial neoplasia or worse lesions (CIN3+) showing an age-adjusted odds ratio (95% confidence interval) of 4.44 (1.26-15.64) and 9.99 (1.30-77.10), respectively. Distinct nucleotide substitutions within Asian lineage including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G were significantly associated with an increased prevalence of HSIL+ and/or CIN3+. It was concluded that non-European variants of HPV16, predominantly Asia variants, had an increased risk of cervical neoplasia relative to European variant.
Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high-grade squamous intraepithelial lesion or worse lesions showing an age-adjusted odds ratio (95% confidence interval) of 5.2 (1.0-27.6) and an increased prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia or more severe lesions with an age-adjusted odds ratio (95% confidence interval) of 7.6 (1.3-43.8). The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation.
Among normal cytological women at study entry, the association between intratypic variants of HPV 16/18/52/58 and risk of incident HSIL and cancer was examined. HPV16 Asian variant at baseline had a 3.15–fold risk to develop HSIL and cervical cancer (95% confidence interval, 0.73-13.57) after adjustment of age, but not statistically significant due to the small number of newly developed cases.
Some studies have documented significant associations of HPV intratypic variants with viral persistent infection, but still limited data concerned. In this study, there were 6,383 women completed follow-up visit from 1993 to 1995. The HPV DNA in their cervical cells was also detected and typed by EasyChip HPV blot. Among these 653 participants determinable for variant analysis, the persistent infection of HPV 16/18/52/58 was determined in 281 subjects who were cytologically normal at baseline examination and attended follow-up examination. HPV 18 Asian-American variant had a similar proportion of persistent infection (55.6%) with the European variant (0%) showing a statistically significant association (p=0.00022) by Fisher exact test. The HPV 58 A1 variant (5.9%) had a lower proportion of persistent infection than the HPV 58 A3 variant (64.7%) showing an odds ratio of 0.08 (95% confidence interval, 0.01-0.71) after adjustment of age and viral load. HPV 18 Asian-American variant and HPV 58 A3 variant have a general tendency to persist more frequently than other variants.
The prevalence of HPV 16/18/52/58 variants and the phylogeny of HPV 52 and HPV 58 in Taiwan were first documented in this report. This study is, to date, the first report of HPV 16/18/52/58 variants associated with viral persistence, or high-grade cytological or histological diagnoses of cervical neoplasia, or incident HSIL and cancer in Taiwan. The variant groups of HPV 16/18/52/58 were associated with different risks of viral persistence or cervical neoplasia.
Subjects
HPV 16
HPV 18
HPV 52
HPV 58
variants
cervical neoplasia
persistent infection
SDGs
Type
thesis
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